PESTICIDE RESIDUES IN FOOD - 1988
Sponsored jointly by FAO and WHO
with the support of the International Programme
on Chemical Safety (IPCS)
EVALUATIONS 1988
PART II - TOXICOLOGY
Joint meeting of the
FAO Panel of Experts on Pesticide Residues
in Food and the Environment
and the
WHO Expert Group on Pesticide Residues
Rome, 19-28 September 1988
The designations employed and the presentation of material in
this publication do not imply the expression of any opinion
whatsoever on the part of the Food and Agriculture Organization
of the United Nations concerning the legal status of any country,
city or area or of its authorities, or concerning the delimitation
of its frontiers or boundaries.
This report contains the collective views of two international
groups of experts and does not necessarily represent the decisions
or the stated policy of the Food and Agriculture Organization of
the United Nations or the World Health Organization.
INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
The preparatory work for the toxicological evaluations of
pesticide residues carried out by the WHO Expert Group on
Pesticide Residues for consideration by the FAO/WHO Joint Meeting
on pesticide Residues in Food and the Environment is actively
supported by the International Programme on Chemical Safety
(IPCS).
The International Programme on Chemical Safety (IPCS) is a joint
venture of the United Nations Environment Programme, the
International Labour Organisation, and the World Health
Organization. One of the main objectives of the IPCS is to carry
out and disseminate evaluations of the effects of chemicals on
human health and the quality of the environment.
M-84
ISBN 92-5 102815-X
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of the United Nations, Via delle Terme di Caracalla,
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(c) FAO 1989
CONTENTS
PART II - TOXICOLOGY
List of those attending the Meeting
Abbreviations
Introduction
Toxicology monographs and monograph addenda
AcephateBromide ionDimethipinEthylenethiourea (ETU)FenitrothionMethacrifos*Paclobutrazold-Phenothrin*TolylfluanidVamidothionVinclozolin
Corregenda to 1982 and 1986 Evaluations
Annex I. Reports and other documents resulting from previous Joint
meetings of the FAO Panel of Experts on Pesticide Residues
in Food and the Environment and WHO Expert Groups on
Pesticide Residues
Annex II. Acceptable daily intakes, residue limits, and guideline
levels proposed at the 1988 Meeting
* First full evaluation
1988 JOINT MEETING OF THE FAO PANEL OF EXPERTS ON PESTICIDE RESIDUES
IN FOOD AND THE ENVIRONMENT AND THE WHO EXPERT GROUP ON PESTICIDE
RESIDUES
Rome, 19-28 September 1988
FAO Panel of Experts on Pesticide Residues in Food and the Environment
Mr J.A.R. Bates, formerly Head, Pesticide Registration and
Surveillance Department, Ministry of Agriculture, Fisheries and
Food, Harpenden, UK.
Professor Dr A.F.H. Besemer, formerly Chair of Phytopharmacy,
Agricultural University, Wageningen, The Netherlands.
Dr R. Greenhalgh, Plant Research Centre, Agriculture Canada,
Ottawa, Canada.
Mr D.J. Hamilton, Assistant Director, Agricultural Chemistry Branch,
Department of Primary Industries, Brisbane, Australia.
Professor E.D. Magallona, Department of Entomology, College of
Agriculture, University of the Philippines at Los Banos College,
Laguna, Philippines.
Mr K. Voldum-Clausen, Division of Chemical Contaminants in Food,
National Food Agency, Soborg, Denmark.
WHO Expert Group on Pesticide Residues
Prof. N.M.S. Bakry, Head, Professor of Pesticide Chemistry and
Toxicology, Faculty of Agriculture, University of Alexandria,
El-Shatby, Alexandria, Egypt.
Dr V. Benes, Chief, Department of Toxicology, Institute of Hygiene and
Epidemiology, 10042 Prague 10, Czechoslovakia.
Dr A.L. Black, Medical Adviser in Toxicology, Department of Community
Services and Health, Woden, Australia.
Mr D.J. Clegg, Head, Agricultural Chemicals Section, Toxicological
Evaluation Division, Food Directorate, Health Protection Branch,
Tunneys Pasture, Ottawa, Ontario, KIA 0L2 Canada.
Prof. M. Lotti, Università di Padova, Istituto di Medicina del Lavoro,
Via Facciolati 71, 35127 Padova, Italy.
Dr O.E. Paynter, Chief Scientist, Hazard Evaluation Division, US
Environmental Protection Agency, Washington, D.C., USA.
Secretariat
Dr Mrs E.P. Arnold, Toxicologist, Agricultural Chemicals Section,
Toxicological Evaluation Division, Health Protection Branch, Health
& Welfare Canada, Ottawa, KIA 0L2 Canada.
(WHO Temporary Adviser)
Prof. C.L. Berry, Department of Morbid Anatomy, The London Hospital
Medical College, Whitechapel, London E1 1.BB, UK.
(WHO Temporary Adviser)
Dr G. Burin, Office of Pesticide Programs, US Environmental Protection
Agency, TS-769 Washington, D.C., 20460 USA.
(WHO Consultant)
Dr J.L. Herrman, International Programme on Chemical Safety, World
Health Organization, 1211 Geneva 27, Switzerland.
(WHO Joint Secretary)
Dr R.B. Jaeger, Toxicologist, Section Head, Special Analyses and
Coordination Branch, Health Effects Division, US Environmental
Protection Agency, Washington, D.C., USA.
(WHO Temporary Adviser)
Dr J. van der Kolk, Foodstuffs Division, Ministry of Welfare, Health
and Cultural Affairs, Rijswijk, Netherlands.
(Chairman of the CCPR)
Dr F.-W. Kopisch-Obuch, Plant Protection Service, Food and Agriculture
Organization, Rome, Italy.
(FAO Joint Secretary)
Dr L.G. Ladomery, Food Standards Officer, Joint FAO/WHO Food Standards
Programme, Food and Agriculture Organization, Rome, Italy.
Mr A.F. Machin, London, England.
(FAO Consultant)
Dr A. Moretto, Università di Padova, Istituto di Medicina del Lavoro,
Padova, Italy.
(WHO Temporary Adviser)
Dr R. Plestina, Division of Vector Biology and Control, World Health
Organization, 1211 Geneva 27, Switzerland.
Dr L. Shuker, Unit of Carcinogen Identification and Evaluation,
International Agency for Research on Cancer, 150 Cours Albert
Thomas, Lyon, Cedex 08 France.
(WHO Temporary Adviser)
Dr A. Takanaka, Head, Division of Pharmacology, Biological Safety
Research Center, National Institute of Hygienic Sciences,
Tokyo, Japan.
(WHO Temporary Adviser)
Dr Mrs. E.M. den Tonkelaar, Toxicology Advisory Center, National
Institute of Public Health and Environmental Protection,
Bilthoven, The Netherlands.
(WHO Temporary Adviser)
Mr M. Walsh, Administrator, E.E.C., Législation des produits végétaux
et de nutrition animale, Brussels, Belgium.
(WHO Temporary Adviser)
ABBREVIATIONS USED IN THESE MONOGRAPHS
2-AAF 2-acetylaminofluorine
AChE acetylcholinesterase
ADI acceptable daily intake
a.i. active ingredient
ALD acute lethal dose
ALP alkaline phosphatase
ALT alanine aminotransferase
AMP aminomethylphosphonic acid
AST aspartate aminotransferase
BUN blood urea nitrogen
bw body weight
CD caesarian derived
ChE cholinesterase
CHO Chinese hamster ovary
CMC carboxymethylcellulose
CNS central nervous system
EMS ethylmethanesulfonate
F1 filial generation, first
F2 filial generation, second
FAO Food and Agriculture Organization of the United Nations
FSH follicle stimulating hormone
GC gas chromatography
GH growth hormone
GI gastrointestinal
GLC gas-liquid chromatography
GMP guanosine monophosphate
GOT glutamate-oxoloacetate transaminase
GPT glutamate-pyruvate transaminase
GSSG glutathione, oxidized
Hb haemoglobin
HGPRT hypoxanthine-guanine phosphoribosyl transferase
HPLC high pressure liquid chromatography
IARC International Agency for Research on Cancer
IBT Industrial Bio-Test Laboratories, Inc.
i.m. intramuscular
i.p. intraperitoneal
IPCS International Programme on Chemical Safety
i.v. intravenous
JMPR Joint FAO/WHO Meeting on Pesticide Residues (Joint Meeting
of the FAO Panel of Experts on Pesticide Residues in Food
and the Environment and a WHO Expert Group on Pesticide
Residues)
LC50 lethal concentration, median
LD50 lethal dose, median
LDH lactate dehydrogensase
MCA 3-methylcholanthrene
MCH mean corpuscular haemoglobin
MCHC mean corpuscular haemoglobin concentration
MCV mean corpuscular volume
mmol/l millimoles/liter
MMS methylmethane sulfonate
MTD maximum tolerated dose
NADPH nicotinamide adenine dinucleotide phosphate (reduced)
ng nanogram
NOAEL no-observed-adverse-effect level
NOEL no-observed-effect level
NPMG N-nitrosophosphonomethyl glycine
NTE neurotoxic esterase
OECD Organization for Economic Cooperation and Development
op organophosphate
2-PAM 2-pyridine aldoxine methyl (pralidoxime)
p.c. post-coitum
p.o. per oral
ppb parts per billion (1000 ppb = 1 ppm)
ppm parts per million
PRL prolactin
RBC red blood cell
RER rough endoplasmic reticulum
s.a. specific activity
SAP serum alkaline phosphatase
s.c. subcutaneous
SCE sister chromatid exchange
SER smooth endoplasmic reticulum
T3 triiodothyronine
T4 thyroxin
TADI temporary acceptable daily intake
TBG thyroxine binding globulin
TEM triethylenemelamine
TLC thin layer chromatography
TLV threshold limit value
TOCP tri-o-cresyl phosphate
TSH thyrotropin
UDS unscheduled DNA synthesis
WBC white blood cell
WHO World Health Organization
w/v weight/volume
&lt less than
&lt less than or equal to
&gt greater than
&gt greater than or equal to
INTRODUCTION
The toxicology monographs and monograph addenda contained in this
volume were prepared by a WHO Expert Group on Pesticide Residues that
met with the FAO Panel of Experts on Pesticide Residues in Food and
the Environment in a Joint Meeting on Pesticide Residues (JMPR) in
Rome, Italy, 19-28 September 1988. These monographs summarize the
safety data on those pesticide residues for which sufficient
information was provided to the WHO Expert Group for it to make
decisions regarding acceptable daily intakes.
Most of the compounds considered by the WHO Expert Group at this
Meeting had been evaluated at previous meetings and monographs on them
have been published previously. In such cases, only new information is
summarized in the relevant "monograph addenda". Reference is made to
reports and other documents resulting from previous Joint Meetings of
the FAO Panel of Experts on Pesticide Residues in Food and the
Environment and WHO Expert Groups on Pesticide Residues, which are
listed in Annex I. The appropriate documents should be consulted to
obtain a full toxicological profile of the chemicals under
consideration.
The report of the Joint Meeting has been published by the Food
and Agriculture Organization (FAO) of the United Nations as FAO Plant
Production and Protection Paper No. 92. The report contains brief
comments on the compounds under consideration, acceptable daily
intakes established by the WHO Expert Group, and maximum residue
limits or guideline levels established by the FAO Panel of Experts.
Residues monographs prepared by the FAO Panel of Experts have been
published as a companion volume to this one: Evaluations 1988, Part I
Residues (FAO Plant Production and Protection Paper No. 93/1).
The toxicology monographs and monograph addenda contained in this
volume are based on working papers that were prepared by temporary
advisers in advance of the 1988 Joint Meeting. A special
acknowledgement is given to those who prepared these working papers:
Dr A. Moretto, University of Padua Medical School, Padua, Italy;
Dr R.B. Jaeger, U.S. Environmental Protection Agency, Washington, DC,
USA; Dr E.M. den Tonkelaar, National Institute of Public Health and
Environmental Protection, Bilthoven, The Netherlands; and
Dr E.P. Arnold, Health & Welfare Canada, Ottawa, Canada.
The preparation and editing of the monographs included in this
volume have been made possible through the technical and financial
contributions of the lead Institutions of the International Programme
on Chemical Safety (IPCS), which support the activities of JMPR. The
designations employed and the presentation of the material in this
publication do not imply the expression of any opinion whatsoever on
the part of the Central Unit of the IPCS concerning the legal status
of any country, territory, city, or area or its authorities, or
concerning the delimitation of its frontiers or boundaries. The
mention of specific companies or of certain manufacturers' products
does not imply that they are endorsed or recommended by the IPCS in
preference to others of a similar nature that are not mentioned.
Any comments or new information on the biological or
toxicological data on the compounds reported in this document should
be addressed to: Joint WHO Secretary of the Joint FAO/WHO Meeting on
Pesticide Residues, International Programme on Chemical Safety, World
Health Organization, Avenue Appia, 1211 Geneva 27, Switzerland.